Disposition of a murine monoclonal antibody vinca conjugate (KS1/4-DAVLB) in patients with adenocarcinomas.
The pharmacokinetics of a murine monoclonal antibody vinca conjugate (KS1/4-DAVLB) was investigated in 13 patients with adenocarcinomas who received single intravenous doses ranging from 40 to 250 mg/m2 and in three patients who were administered 1.5 mg/kg every 48 to 72 hours for up to 15 doses. Five patients in the single-dose study also received 100 microCi of [3H]-KS1/4-DAVLB. Overall mean values for the pharmacokinetic variables were as follows: elimination half-life, 31.5 hours; distribution volume, 4.43 L; and clearance, 0.09 L/hr. KS1/4-DAVLB demonstrated linear elimination kinetics in both the single- and multiple-dose studies. Significant concentrations of KS1/4-DAVLB were noted in a pleural effusion. Ten percent of the radioactive dose was recovered in the urine and 20% in the feces over a 5-day period. Small molecular weight vinca species were detected in the feces but not in the serum.
Schneck
D
D
Lilly Laboratories for Clinical Research, Eli Lilly Co., Indianapolis, IN.
Butler
F
F
Dugan
W
W
Littrell
D
D
Petersen
B
B
Bowsher
R
R
DeLong
A
A
Dorrbecker
S
S
D000230:Adenocarcinoma / Q000097:blood / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms / Q000097:blood / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D006207:Half-Life; D006801:Humans; D015592:Immunoradiometric Assay; D000922:Immunotoxins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000097:blood / Q000378:metabolism*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C052417:4-desacetylvinblastine-monoclonal antibody KS1-4 conjugate; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D014747:Vinblastine